title: Polysialylation promotes neural cell adhesion molecule-mediated cell migration in a fibroblast growth factor receptor-dependent manner, but independent of adhesion capability.
abstract: Polysialic acid (PSA), a carbohydrate polymer mainly present in the neural cell adhesion molecule (NCAM), promotes neural plasticity; however, its mode of action in tumor malignancy remains largely unknown. In this study, we investigated the influence of polysialylation on cell migration. PSA consistently promoted cell migration on different extracellular matrices (ECMs) but differentially affected cell adhesion. All of these actions were reversed by endo-N-acetylneuraminidase treatment, and PSA-driven migration was inhibited by the specific fibroblast growth factor receptor (FGFR) inhibitor Su5402. Consistent with this latter observation, PSA-stimulated migration on different ECMs was paralleled by activation of the FGFR and its downstream signaling components, PLC-γ, focal adhesion kinase and extracellular signal-regulated kinase 1/2. In contrast, the pattern of p59(fyn) activation correlated with differential adhesion to different ECMs. Collectively, these results indicate that PSA-conjugated NCAM potentiates signal transduction by the FGFR pathway and thereby enhances cell migration independent of adhesion capability, providing additional insights into the role of PSA in cancer development.
authors.affiliation: Department of Pharmacology and Glycobiology, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Gong
authors.initials: G
authors.lastname: Dai
authors.forename: Ya-Bin
authors.initials: YB
authors.lastname: Cheng
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Geng
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D051379:Mice; D041681:NIH 3T3 Cells; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019006:Neural Cell Adhesion Molecules; D011758:Pyrroles; D017468:Receptors, Fibroblast Growth Factor; C105686:SU 5402; D012794:Sialic Acids; C021319:polysialic acid